Correlation between Ca Release and Osteoconduction by 3D-Printed Hydroxyapatite-Based Templates.

The application of hydroxyapatite (HA)-based templates is quite often seen in bone tissue engineering since that HA is an osteoconductive bioceramic material, which mimics the inorganic component of mineralized tissues. However, the reported osteoconductivity varies in vitro and in vivo, and the levels of calcium (Ca) release most favorable to osteoconduction have yet to be determined. In this study, HA-based templates were fabricated by melt-extrusion 3D-printing and characterized in order to determine a possible correlation between Ca release and osteoconduction. The HA-based templates were blended with poly(lactide-co-trimethylene carbonate) (PLATMC) at three different HA ratios: 10, 30, and 50%. The printability and physical properties of the HA templates were compared with those of pristine PLATMC. In vitro, osteoconductivity was assessed using seeded human bone marrow-derived mesenchymal stem cells. A mild rate of Ca release was observed for HA10 templates, which exhibited higher mineralized extracellular matrix (ECM) secretion than PLATMC at 14 and 21 days. In contrast, the high rate of Ca release exhibited by HA30 and HA50 templates was associated with reduced osteoconduction and impeded mineralized ECM secretion in vitro. Similar results were observed in vivo. In the calvarial defect model in rabbit, PLATMC and HA10 templates exhibited the highest amount of new bone formation, with obvious contact osteogenesis on their surfaces. In contrast, HA30 and HA50 exhibited distant osteogenesis and reduced amounts of new bone ingrowth. It is concluded that HA-based templates are osteoconductive only at low rates of Ca release.

The Evaluation of Ordinal Regression Model's Performance Through the Implementation of Multilayer Feed-Forward Neural Network: A Case Study of Hypertension.

Background Hypertension, or high blood pressure, is a common medical condition that affects a significant portion of the global population. It is a major risk factor for cardiovascular diseases (CVD), stroke, and kidney disorders. Objective The objective of this study is to create and validate a model that combines bootstrapping, ordered logistic regression, and multilayer feed-forward neural networks (MLFFNN) to identify and analyze the factors associated with hypertension patients who also have dyslipidemia. Material and methods A total of 33 participants were enrolled from the Hospital Universiti Sains Malaysia (USM) for this study. In this study, advanced computational statistical modeling techniques were utilized to examine the relationship between hypertension status and several potential predictors. The RStudio (Posit, Boston, MA) software and syntax were implemented to establish the relationship between hypertension status and the predictors. Results The statistical analysis showed that the developed methodology demonstrates good model fitting through the value of predicted mean square error (MSE), mean absolute deviance (MAD), and accuracy. To evaluate model fitting, the data in this study was divided into distinct training and testing datasets. The findings revealed that the results strongly support the superior predictive capability of the hybrid model technique. In this case, five variables are considered: marital status, smoking status, systolic blood pressure, fasting blood sugar levels, and high-density lipoprotein levels. It is important to note that all of them affect the hazard ratio: marital status (ß1, -17.12343343; p < 0.25), smoking status (ß2, 1.86069121; p < 0.25), systolic blood pressure (ß3, 0.05037332; p < 0.25), fasting blood sugar (ß4, -0.53880322; p < 0.25), and high-density lipoprotein (ß5, 5.38065556; p < 0.25). Conclusion This research aims to develop and extensively evaluate the hybrid approach. The statistical methods employed in this study using R language show that regression modeling surpasses R-squared values in predicting the mean square error. The study's conclusion provides strong evidence for the superiority of the hybrid model technique.

Knowledge and practices of radiation protection among Malaysian radiographers working in nuclear medicine: A preliminary study.

This study is aimed to determine knowledge and practices on radiation protection among radiographers in nuclear medicine department. A cross-sectional survey was conducted among radiographers in nuclear medicine departments in four health institutions in Malaysia. A set of questionnaires was distributed to 17 respondents using convenience sampling. Approximately more than 75% and 44% - 56% of the radiographers have good knowledge of radiation protection and frequent adherence to radiation protection practices, respectively. Levels of education and length of service were statistically correlated with radiation protection knowledge and practices attributes (p < 0.05), respectively. More training is necessary for knowledge and practice improvement.

Repair of a Late Presentation Thoracic Aortic Aneurysm following Coarctation Repair.

We report the case of a 44-year-old gentleman who underwent coarctation repair at the age of 7 years. He was lost to follow-up and represented. Computed tomography scan demonstrated a 9.8-cm diameter aortic aneurysm involving the distal aortic arch and proximal descending aorta. Open surgery was performed to repair the aneurysm. The patient made an unremarkable recovery. He was followed up 12 weeks later, and significant improvement in preoperative symptoms was observed. This case demonstrates the importance of long-term follow-up.

Tartrate resistant acid phosphatase 5 (TRAP5) mediates immune cell recruitment in a murine model of pulmonary bacterial infection.

Introduction: During airway infection, upregulation of proinflammatory cytokines and subsequent immune cell recruitment is essential to mitigate bacterial infection. Conversely, during prolonged and non-resolving airway inflammation, neutrophils contribute to tissue damage and remodeling. This occurs during diseases including cystic fibrosis (CF) and COPD where bacterial pathogens, not least Pseudomonas aeruginosa, contribute to disease progression through long-lasting infections. Tartrate-resistant acid phosphatase (TRAP) 5 is a metalloenzyme expressed by alveolar macrophages and one of its target substrates is the phosphoglycoprotein osteopontin (OPN). Methods: We used a knockout mouse strain (Trap5-/-) and BALB/c-Tg (Rela-luc)31Xen mice paired with siRNA administration or functional protein add-back to elucidate the role of Trap5 during bacterial infection. In a series of experiments, Trap5-/- and wild-type control mice received intratracheal administration of P.aerugniosa (Xen41) or LPS, with mice monitored using intravital imaging (IVIS). In addition, multiplex cytokine immunoassays, flow cytometry, multispectral analyses, histological staining were performed. Results: In this study, we found that Trap5-/- mice had impaired clearance of P. aeruginosa airway infection and reduced recruitment of immune cells (i.e. neutrophils and inflammatory macrophages). Trap5 knockdown using siRNA resulted in a decreased activation of the proinflammatory transcription factor NF-κB in reporter mice and a subsequent decrease of proinflammatory gene expression. Add-back experiments of enzymatically active TRAP5 to Trap5-/- mice restored immune cell recruitment and bacterial killing. In human CF lung tissue, TRAP5 of alveolar macrophages was detected in proximity to OPN to a higher degree than in normal lung tissue, indicating possible interactions. Discussion: Taken together, the findings of this study suggest a key role for TRAP5 in modulating airway inflammation. This could have bearing in diseases such as CF and COPD where excessive neutrophilic inflammation could be targeted by pharmacological inhibitors of TRAP5.

Cerebellar hemorrhage in a healthy young adult: a case report.

BACKGROUND: Cavernous venous malformation is an uncommon entity that occurs in around 0.5% of the general population. Cerebellar cavernous venous malformation accounts for 1.2-11.8% of intracranial cavernous venous malformation cases. Patients are commonly asymptomatic until a hemorrhage occurs. In approximately 20% of the cases, cavernous venous malformation and developmental venous anomalies occur together, called mixed vascular malformation. Our case report reveals the imaging features of the mixed vascular malformation and highlights the appropriate imaging modality and sequence to detect the abnormalities. CASE PRESENTATION: We report the case of a 15-year-old Malay male, a healthy young male who presented with dizziness, vomiting, and mild headache for 1 month. Computed tomography brain imaging at presentation revealed cerebellar hemorrhage with multiple cavernous venous malformation and coexisting developmental venous anomalies, which was then confirmed by magnetic resonance imaging. The patient was started on dexamethasone 4 mg four times a day, observed in the ward, and discharged well without neurological sequelae. CONCLUSION: A cavernous malformation with concurrent developmental venous anomalies requires accurate diagnosis. Our case report contributes to the literature on the imaging diagnosis of this disease, which is beneficial for current and future reference.

Cyclooxygenase-2 immunohistochemical expression is associated with worse prognosis in breast cancer: Retrospective study and literature review.

OBJECTIVES: To assess the immunohistochemistry phenotype of cyclooxygenase-2 (COX-2) in breast cancer (BC) and to correlate it with histological and clinical prognostic factors. METHODS: This retrospective study utilized COX-2 monoclonal antibody in an immunohistochemistry staining of tissue microarrays slides of 570 cases of previously diagnosed BC and with 52 of normal breast tissues from breast specimens resected for benign lesions or reconstruction (fibroadenoma and normal breast epithelium). This project was carried out in the Laboratory of pathology, King Abdulaziz University, Jeddah, Saudi Arabia, between September 2019 and September 2021. RESULTS: The present data showed an important connection between the COX-2 expression phenotype and BC compared to benign breast tissues (p=0.034). The expression pattern of COX-2 was allied significantly with some factors which distinguished aggressive subtypes of BC, such as stage, distant metastases, lymphovascular invasion, and poor survival. CONCLUSION: Cyclooxygenase-2 is a valuable marker that could facilitate BC diagnosis and prognosis.

Sporadic malignant peripheral nerve sheath tumour (MPNST) in a 3-year-old girl: A diagnostic challenge.

INTRODUCTION: Malignant peripheral nerve sheath tumour (MPNST) is an uncommon malignant neoplasm of childhood with unfavourable prognosis. Only a limited number of cases have been reported in children less than 12 years of age, and approximately one-half arise from a benign peripheral nerve sheath tumour, especially in the background of neurofibromatosis type 1 (NF1). Primary MPNST in children is even rarer. CASE REPORT: A 3-year-old Malay girl presented with painful right axillary swelling for six months, initially treated as axillary lymphadenitis and she defaulted follow up. She came back four months later with enlargement of the swelling. The previous biopsy was reported as Schwannoma, which correlates with a benign peripheral nerve sheath tumour's MRI findings. The final diagnosis after debulking surgery was consistent with MPNST. She succumbed to death 20 months after her initial diagnosis of advanced MPNST and lung metastasis. PATHOLOGICAL FINDINGS: Grossly, a huge partly circumscribed soft tissue mass was noted arising from a nerve with a solid greyish yellowish myxoid cut surface. Spindle-shaped cells arranged in a herringbone pattern alternated with areas of myxoid hypocellular areas exhibited marked pleomorphism, brisk mitosis, and extensive necrosis are seen microscopically. Immunohistochemistry shows patchy S100 protein staining with loss of expression of H3K27me3. CONCLUSION: Although MPNST is rare in the paediatric age group, the diagnosis should be considered in children without NF1 with a rapidly evolving and painful mass in the peripheral nerve distribution. In this case, the diagnosis was delayed and made after surgery. Due to its morphologic heterogeneity and lack of specific immunohistochemical markers, MPNST remains a diagnostic challenge.

Incidence and Predictors of Surgical Site Infection Complications in Diabetic Patients Undergoing Lower Limb Amputation.

BACKGROUND: Surgical site infections (SSIs) following lower extremity amputations (LEAs) are a major cause of patient morbidity and mortality. The objectives of this study are to investigate the annual incidence of SSI and risk factors associated with SSI after LEA in diabetic patients. METHODS: LEAs performed on diabetic patients between 2005 and 2017 were retrospectively analyzed from the American College of Surgeons National Surgical Quality Improvement Program database. Incidence rates were calculated and analyzed for temporal change. Multivariable logistic regression was conducted to identify the independent predictors of SSIs in LEA. RESULTS: In 21,449 diabetic patients, the incidence of SSIs was 6.8% after LEA, with an overall decreasing annual trend (P = 0.013). Amputation location (below-knee in reference to above-knee) [OR (95% CI): 1.35 (1.20 - 1.53), P <0.001], smoking [OR (95% CI): 1.25 (1.11 - 1.41), P <0.001)], female sex [OR (95% CI): 1.16 (1.03 - 1.30)], preoperative sepsis [OR (95% CI): 1.24 (1.10 - 1.40), P <0.001], P = 0.013], emergency status [OR (95% CI): 1.38 (1.17 - 1.63), P <0.001], and obesity [OR (95% CI): 1.59 (1.12 - 2.27), P = 0.009] emerged as independent predictors of SSIs, while moderate/severe anemia emerged as a risk-adjusted protective factor [OR (95% CI): 0.75 (0.62 - 0.91), P = 0.003]. Sensitivity analysis found that moderate/severe anemia, not body mass index (BMI) class, remained a significant risk factor in the development of SSIs in below-the-knee amputations; in contrast, higher BMI, not preoperative hematocrit, was significantly associated with an increased risk for SSI in above-the-knee amputations. CONCLUSIONS: The incidence of SSIs after LEA in diabetic patients is decreasing. Overall, below-knee amputation, smoking, emergency status, and preoperative sepsis appeared to be associated with SSIs. Obesity increased SSIs in above-the-knee amputations, while moderate/severe preoperative anemia appears to protect against below-the-knee SSIs. Surgeons should take predictors of SSI into consideration while optimizing care for their patients, and future studies should investigate the role of preoperative hematocrit correction and how it may influence outcomes positively or negatively.

Meningioma genomics: a therapeutic challenge for clinicians.

Meningiomas are amongst the most commonly encountered intracranial tumors. The majority of these tumors arise intracranially, and the remaining incidents occur along the spinal cord. Meningiomas tend to grow gradually, with many tumors arising in inaccessible locations. Such sporadic behavior poses a therapeutic challenge to clinicians, causing incomplete tumor resections that often lead to recurrence. Therefore, ongoing research seeks to find alternative systematic treatments for meningiomas, with gene-based therapeutics of high interest. Subsequently, genetic studies characterized frequent somatic mutations in NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA. These genes are communally exhibited in 80% of sporadic meningiomas. In addition, other genes such as the DUSP family, the NR4 family, CMKOR, and FOSL2, have been identified as key players in spinal meningiomas. In this perspective, we aim to investigate current genetic-based studies, with the ongoing research mainly focused on the above NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA genes and their involved pathways. In addition, this perspective can serve as a potential cornerstone for future genetic analyses of meningioma cases.

Application of a new system for classifying root and canal anatomy in studies involving micro-computed tomography and cone beam computed tomography: Explanation and elaboration.

Adequate knowledge and accurate characterization of root and canal anatomy is an essential prerequisite for successful root canal treatment and endodontic surgery. Over the years, an ever-increasing body of knowledge related to root and canal anatomy of the human dentition has accumulated. To correct deficiencies in existing systems, a new coding system for classifying root and canal morphology, accessory canals and anomalies has been introduced. In recent years, micro-computed tomography (micro-CT) and cone beam computed tomography (CBCT) have been used extensively to study the details of root and canal anatomy in extracted teeth and within clinical settings. This review aims to discuss the application of the new coding system in studies using micro-CT and CBCT, provide a detailed guide for appropriate characterization of root and canal anatomy and to discuss several controversial issues that may appear as potential limitations for proper characterization of roots and canals.

Hypothalamic Hamartomas: A comprehensive review of literature - Part 2: Medical and surgical management update.

Hypothalamic hamartomas (HH) are rare, non-neoplastic heterotopic tissues which contains normal neurons and glia including oligodendrocytes and fibrillary astrocytes but in an abnormal distribution. They arise from the floor of the third ventricle, tuber cinereum, or mammillary bodies. Estimated incidence ranges from 1 in 50,000 to 1 in 1,000,000. Hypothalamic hamartomas are associated with different clinical presentations including various types of seizures, most characteristically; the gelastic seizures, precocious puberty, cognitive impairment and behavioral changes. In this review, the authors discuss the recent advancements in the medical and surgical management of hypothalamic hamartoma that have been achieved over the past few decades. This review also discusses the advantages and disadvantages of each surgical line of management and factors determining the best individualized approach.

Impact of a Central-Line Insertion Site Assessment (CLISA) score on localized insertion site infection to prevent central-line-associated bloodstream infection (CLABSI).

OBJECTIVE: To assess the impact of a newly developed Central-Line Insertion Site Assessment (CLISA) score on the incidence of local inflammation or infection for CLABSI prevention. DESIGN: A pre- and postintervention, quasi-experimental quality improvement study. SETTING AND PARTICIPANTS: Adult inpatients with central venous catheters (CVCs) hospitalized in an intensive care unit or oncology ward at a large academic medical center. METHODS: We evaluated CLISA score impact on insertion site inflammation and infection (CLISA score of 2 or 3) incidence in the baseline period (June 2014-January 2015) and the intervention period (April 2015-October 2017) using interrupted times series and generalized linear mixed-effects multivariable analyses. These were run separately for days-to-line removal from identification of a CLISA score of 2 or 3. CLISA score interrater reliability and photo quiz results were evaluated. RESULTS: Among 6,957 CVCs assessed 40,846 times, percentage of lines with CLISA score of 2 or 3 in the baseline and intervention periods decreased by 78.2% (from 22.0% to 4.7%), with a significant immediate decrease in the time-series analysis (P < .001). According to the multivariable regression, the intervention was associated with lower percentage of lines with a CLISA score of 2 or 3, after adjusting for age, gender, CVC body location, and hospital unit (odds ratio, 0.15; 95% confidence interval, 0.06-0.34; P < .001). According to the multivariate regression, days to removal of lines with CLISA score of 2 or 3 was 3.19 days faster after the intervention (P < .001). Also, line dwell time decreased 37.1% from a mean of 14 days (standard deviation [SD], 10.6) to 8.8 days (SD, 9.0) (P < .001). Device utilization ratios decreased 9% from 0.64 (SD, 0.08) to 0.58 (SD, 0.06) (P = .039). CONCLUSIONS: The CLISA score creates a common language for assessing line infection risk and successfully promotes high compliance with best practices in timely line removal.

Long-term survival following on-pump and off-pump coronary artery bypass graft surgery: a propensity score-matched analysis.

OBJECTIVES: Recent studies have once again brought into focus the long-term survival following off-pump coronary artery bypass grafting (OPCAB) compared with conventional on-pump coronary artery bypass grafting surgery (ONCAB). The aim of this study was to compare the long-term risk-adjusted survival rates in patients undergoing coronary artery bypass grafting (CABG) using these 2 techniques. METHODS: We undertook a propensity score-matched analysis of 10 293 patients who underwent CABG at our single institution between 2000 and 2016. A logistic regression model was fitted using 14 covariates and their 2-way interactions to calculate an estimated propensity score [area under curve (AUC) 0.69], from which 1:1 nearest neighbour matching was performed. Patient survival was assessed using the Kaplan-Meier method and log-rank test. RESULTS: Of the total cohort, 8319 patients had ONCAB and 1974 had OPCAB. Prior to matching, the OPCAB group had marginally higher EuroSCORE [3.7 ± 2.7 vs 3.5 ± 3, median (interquartile range) 3 (2-5) vs 3 (2-5), P = 0.016] and significantly lower average number of grafts per patient (2.39 ± 0.72 vs 2.75 ± 0.48, P < 0.001). Post-matching distributions between OPCAB and ONCAB showed a substantial improvement in balance in preoperative patient characteristics. The 2 surgery groups differed significantly in survival (P < 0.001). OPCAB demonstrated improved long-term survival at 10 years [84.8%, 95% confidence interval (CI) (82.7-86.9%) vs 75.8%, 95% CI (73.4-78.2%)] and 15 years [65.4%, 95% CI (61.4-69.6%) vs 58.5%, 95% CI (54.9-62.3%)]. Results of sensitivity analysis for 1:2 and 1:3 matched data were in concordance with these findings of survival. CONCLUSION: At our institution, selected patients who underwent OPCAB had lower in-hospital morbidity and improved long-term survival when compared with a matched population of ONCAB patients.

Osteopontin Expression in Small Airway Epithelium in Copd is Dependent on Differentiation and Confined to Subsets of Cells.

Osteopontin (OPN) plays a role in inflammation via recruitment of neutrophils and tissue remodeling. In this study, we investigated the distribution of OPN-expressing cells in the airway epithelium of normal lung tissue and that from patients with chronic obstructive pulmonary disease (COPD). OPN was detected on the epithelial cell surface of small airways and in scattered cells within the epithelial cell layer. Staining revealed higher OPN concentrations in tissue showing moderate to severe COPD compared to that in controls. In addition, OPN expression was confined to goblet and club cells, and was absent from ciliated and basal cells as detected via immunohistochemistry. However, OPN expression was up-regulated in submerged basal cells cultures exposed to cigarette smoke (CS) extract. Cell fractioning of air-liquid interface cultures revealed increased OPN production from basal compartment cells compared to that in luminal fraction cells. Furthermore, both constitutive and CS-induced expression of OPN decreased during differentiation. In contrast, cultures stimulated with interleukin (IL)-13 to promote goblet cell hyperplasia showed increased OPN production in response to CS exposure. These results indicate that the cellular composition of the airway epithelium plays an important role in OPN expression and that these levels may reflect disease endotypes in COPD.

The Influence of Tibial Tuberosity-trochlear Groove Distance on Development of Patellofemoral Pain Syndrome.

Background: Tibial tuberosity-trochlear groove distance (TT-TGD) measurements play a decisive role in evaluating patellofemoral joint disorders. However, the prevalence of pathological TT-TGD among patients with patellofemoral pain remains unclear. The purpose of this study was to compare the size of TT-TGD among patients with patellofemoral pain syndrome (PFPS) and those with no history of patellofemoral pain. Methods: A total of 100 cases participated in this case-control study, among whom 53 individuals were in the case group and 47 individuals were in the control group. TT-TGD was measured by magnetic resonance imaging. Results: The mean TT-TGD was 12.3±3.3 in patients and 9.3±2.4 in controls (P<0.001). Among patients, we had totally 34 patients with TT-TG equal or lower than 13 (64.2%) and in 18 patients, it was higher than 13 (34%). Conclusion: The mean TT-TGD in patients with PFPS was greater than that in the control group (P=0.001). An increase in TT-TGD can be considered one of the factors behind the development of PFPS.

Has Publishing Surgeon-Specific Outcomes Had an Impact on Training in Cardiac Surgery?

BACKGROUND: Surgeon-specific outcome data are now published for most surgical specialties in the United Kingdom. There are concerns that this initiative has had a negative impact on training. The primary objective of this study was to assess whether training activity has changed since the publication of surgeon-specific outcomes in cardiac surgery. METHODS: Prospectively collected data for cardiac surgical procedures performed at a single center from 2004 to 2016 were analyzed. The cohort was split into two halves according to operation date. Multivariable logistic regression was used to assess whether training activity had increased from the first to the second part of the study and to identify whether trainee first operator was associated with adverse outcomes. RESULTS: A total of 14,054 cardiac surgical procedures were included, of which 1,777 (12.6%) had a trainee as first operator. Despite an increase in the risk profile of patients undergoing surgical procedures, the proportion of cases performed by trainees increased from 11.7% (786 of 6,708) in the first half of the study to 13.5% (991 of 7,346) in the second half of the study (p = 0.002). This effect remained after adjustment for confounding variables. Trainee first operator was not significantly associated with an increased risk of any adverse short-term outcome. CONCLUSIONS: Since surgeon-specific outcome publication began in United Kingdom, cardiac surgical training activity has significantly increased at the study center despite an increase in the risk profile of patients. This study demonstrates that it is possible to maintain or even increase training activity with good outcomes in the era of surgeon-specific outcome publication.

Osteopontin protects against lung injury caused by extracellular histones.

Extracellular histones are present in the airways because of cell death occurring during inflammation. They promote inflammation and cause tissue damage due to their cationic nature. The anionic phosphoglycoprotein osteopontin (OPN) is expressed at high levels during airway inflammation and has been ascribed both pro- and anti-inflammatory roles. In this study, it was hypothesized that OPN may neutralize the harmful activities of extracellular histones at the airway mucosal surface. In a model of histone-induced acute lung injury, OPN-/- mice showed increased inflammation and tissue injury, and succumbed within 24 h, whereas wild-type mice showed lower degrees of inflammation and no mortality. In lipopolysaccharide-induced acute lung injury, wild-type mice showed less inflammation and tissue injury than OPN-/- mice. In bronchoalveolar lavage fluid from ARDS patients, high levels of OPN and also histone-OPN complexes were detected. In addition, OPN bound to histones with high affinity in vitro, resulting in less cytotoxicity and reduced formation of tissue-damaging neutrophil extracellular traps (NETs). The interaction between OPN and histones was dependent on posttranslational modification of OPN, i.e., phosphorylation. The findings demonstrate a novel role for OPN, modulating the pro-inflammatory and cytotoxic properties of free histones.

TFPI-2 Protects Against Gram-Negative Bacterial Infection.

Tissue factor pathway inhibitor-2 (TFPI-2) has previously been characterized as an endogenous anticoagulant. TFPI-2 is expressed in the vast majority of cells, mainly secreted into the extracellular matrix. Recently we reported that EDC34, a C-terminal peptide derived from TFPI-2, exerts a broad antimicrobial activity. In the present study, we describe a previously unknown antimicrobial mode of action for the human TFPI-2 C-terminal peptide EDC34, mediated via binding to immunoglobulins of the classes IgG, IgA, IgE, and IgM. In particular the interaction of EDC34 with the Fc part of IgG is of importance since this boosts interaction between the immunoglobulin and complement factor C1q. Moreover, we find that the binding increases the C1q engagement of the antigen-antibody interaction, leading to enhanced activation of the classical complement pathway during bacterial infection. In experimental murine models of infection and endotoxin challenge, we show that TFPI-2 is up-regulated in several organs, including the lung. Correspondingly, TFPI-2-/- mice are more susceptible to pulmonary Pseudomonas aeruginosa bacterial infection. No anti-coagulant role of TFPI-2 was observed in these models in vivo. Furthermore, in vivo, the mouse TFPI-2-derived C-terminal peptide VKG24, a homolog to human EDC34 is protective against systemic Escherichia coli bacterial infection. Moreover, in sputum from cystic fibrosis patients TFPI-2 C-terminal fragments are generated and found associated with immunoglobulins. Together our data describe a previously unknown host defense mechanism and therapeutic importance of TFPI-2 against invading Gram-negative bacterial pathogens.

Sodium pentosan polysulfate efficacy as thromboprophylaxis agent in high-risk women following gynecological surgery.

AIM: Sodium pentosan polysulfate (Na-PPS) is a plant-based agent that has similar action with low-molecular-weight heparin. It inhibits factor Xa, preventing blood clot formation. To date, its use in clinical practice as thromboprophylaxis agent is still limited. In addition, the efficacy and safety profile of this agent was not robustly reported globally, especially for countries with major Muslim population. We hypothesized that Na-PPS was equally effective as the standard thromboprophylaxis. We aim to compare the efficacy and safety of Na-PPS against standard agent (fondaparinux or enoxaparin). METHODS: This was a randomized control, open-label trial. Women underwent major gynecological surgery were randomized to receive either subcutaneous 50 mg of Na-PPS twice daily or subcutaneous enoxaparin 40 mg once daily. Fondaparinux 2.5 mg once daily was given to Muslim women as an alternative to enoxaparin. The treatment was started 6 h postoperatively, for at least 3 days. All the patients received thromboembolic deterrent stockings. The primary efficacy outcome was venous thromboembolism up to 3 days postsurgery. The main safety outcomes were minor and major bleeding. RESULTS: Among 109 participants, there was no incidence of venous thromboembolism. None of the women developed major bleeding. Minor bleeding was observed in 28.3% (15/53) and 5.4% (3/56) of Na-PPS and standard thromboprophylaxis group, respectively (P = 0.001). CONCLUSION: Na-PPS was associated with increased risk of minor bleeding. There was insufficient data to conclude its efficacy as thromboprophylaxis. Further research is needed to evaluate Na-PPS safety as a standard thromboprophylactic agent.